Resection Margin Research Articles

Metanephrine mirage: distinguishing the phaeocopies, a case report and literature review.

We present one of only seven reported cases of a catecholamine-secreting adrenal neuroblastoma in an adult. The case is used as a platform to discuss key biochemical, genomic and imaging considerations that are central to the successful, targeted management of catecholamine-secreting adrenal tumours. A 63-year-old male was urgently reviewed at a tertiary hospital endocrinology outpatient clinic for a 12cm right-sided adrenal incidentaloma. Plasma normetanephrine and 3-methoxytyramine levels were approximately 10 times the upper limit of normal at 9272pmol/L (< 900) and 1023pmol/L (< 110), respectively. The adrenal mass appeared to be inseparable from the liver on imaging, and thus wassuspected to be an invasive malignant phaeochromocytoma. FDG positron emission tomography (PET)/CT demonstrated moderate to intense metabolic activity within the right adrenal mass. [68Ga]Ga-DOTATATE (Ga-TATE) PET-CT demonstrated patchy, heterogenous somatostatin receptor (SSTR) expression in the adrenal lesion, at most Krenning 3 (intensity above liver). The patient underwent a right adrenalectomy and segment 6/7 liver resection. Histopathology revealed a 130mm diameter neuroblastoma of the differentiating subtype with a low Mitosis-Karyorrhexis Index. There was lymphovascular invasion and tumour focally present at the resection margin, but no tumour in one periadrenal lymph node, and no tumour invasion in the adherent liver. Immunohistochemistry revealed ALK positivity (+ 3) and wild type ATRX. At nine months following adrenalectomy, the plasma normetanephrine level has reduced to 991pmol/L (< 900). Post-operative GaTate PET/CT shows no definite abnormal SSTR-expressing lesions in the surgical bed or elsewhere. The patient has completed adjuvant radiotherapy and is a candidate for ALK-targeted therapy if required for recurrence in the future. Neuroblastomas may be misdiagnosed as phaeochromocytomas given the ability to secrete catecholamines and similarities in radiological appearance. Differentiating neuroblastomas from phaeochromocytomas and paragangliomas (PPGL) is critical, but clinically difficult. Genomics are central for management; diagnosing ALK-positive neuroblastoma triggers consideration of ALK-targeted therapy, which is not relevant for PPGL. A critical eye is required for the accurate diagnosis and management of malignant adrenal incidentalomas.

Pitfalls of frozen section diagnosis in ureter margin evaluation of plasmacytoid urothelial carcinoma of urinary bladder.

Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive subtype that often presents at advanced stages with poor prognosis. This study investigated tumor invasion to better understand tumor behavior and potentially to improve management strategies by comparing the clinicopathologic characteristics of PUC with positive ureter resection margin (+ URM) with PUC with negative URMs (-URM). This retrospective analysis used pathology reports from 2017 to 2023 for cases diagnosed with PUC during radical cystectomy (RC). All applicable H&E slides of RC specimens were reviewed. Cases with a plasmacytoid component greater than 25% in the RC specimens were analyzed. Frozen section analyses (FSAs) and permanent section analyses (PSAs) of ureter resection margins were performed. Fifteen patients with a plasmacytoid component greater than 25% in their RC specimens were identified. Compared with -URM PUC cases, +URM PUC cases were located more frequently at the trigone or bladder neck, and all + URM cases exhibited ureter orifice involvement. Among 6 PSA-positive cases, three (50%) cases showed discrepancies with FSA. Three + URM cases exhibited PUC tumor cells along the submucosa and muscularis propria layer, and the 3 remaining cases showed PUC tumor cells along the adventitia. We observed a consistent adventitia invasion in all the discordant cases, with sectioning errors and misinterpretation identified as the primary causal factors. To the best of our knowledge, this is the first study to demonstrate two separate patterns of tumor infiltration along the ureter and to discuss the significance of comparing FSA with PSA in PUC. The significance of comprehensive management strategies for PUC patients, including a thorough evaluation of ureteral margins and accurate interpretation of periureteral fat tissue, is highlighted. Large, well-designed studies are needed to strengthen the evidence and to establish optimal management strategies for patients with PUC.

Nomogram for predicting early recurrence of hepatocellular carcinoma with narrow resection margin.

Narrow resection margin hepatocellular carcinoma (NRM-HCC) has a high incidence of early recurrence. Our study was designed to identify prognostic factors in patients with NRM-HCC, establish and validate a nomogram model to predict early recurrence of NRM-HCC patients. We retrospectively analyzed data from 2957 NRM-HCC patients who underwent radical hepatectomy at three medical centers between December 2009 and January 2015. Patients were randomly assigned to a training cohort (n = 2069) and a validation cohort (n = 888). Using univariate and multivariate COX regression to determine early relapse factors in NRM-HCC patients, and used these factors to construct a nomogram. The accuracy of the prediction was evaluated using the C-index, receiver operating characteristic (ROC) and calibration curve. Decision curve analysis (DCA) assessed the predictive value of the models. Finally, the recurrence-free survival of different risks was analyzed using Kaplan-Meier (K-M) method. The nomogram of NRM model contains alpha-fetoprotein (AFP), alkaline phosphatase (ALP), tumor size, tumor number, microvascular invasion (MVI), tumor capsular, and satellite nodules. The model shows good discrimination with C-indexes of 0.71 (95% CI: 0.69-0.72) and 0.72 (95% CI: 0.70-0.75) in the train cohort and test cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different early recurrence. The web-based tools are convenient for clinical practice. NRM model demonstrated favorable performance in predicting early recurrence in NRM-HCC patients. This novel model will be helpful to guide postoperative follow-up and adjuvant therapy.

OGC SO33 - Resection Margins in Gastrectomy Patients – Are Current Guidelines Fit for Purpose? An Observational Study from a Tertiary Centre

Abstract Background Positive resection margins in cancer surgery are associated with higher likelihood of locoregional recurrence and poor outcomes. The Association of Upper GI Surgeons (AUGIS) outlined a target of less than 5% margin positivity for gastric resections, a goal not met in repeated national audits (NOGCA). Our study aimed to evaluate the positive resection margin rate after a gastrectomy in a tertiary centre and identify associated factors to assess the current guideline's suitability. Our hypothesis is that positive longitudinal margins are more related to tumour factors, such as proximity to the intended margin, rather than poor surgical technique. Method All records of patients who underwent gastrectomy from June 2015 to September 2021 were retrospectively reviewed. Data collection included demographic details, type of gastrectomy, exposure to neoadjuvant chemotherapy, and post operative histopathological information such as tumour differentiation, presence of signet ring (SR) morphology and linitis-plastica (LP), and resection margin(RM) status. Chi square tests of association were utilised to determine associations between the resection margin status and the potential determinant factors. Results Our study included 144 subjects (100 males, mean age 66, range 27-87). Types of gastrectomy were subtotal (38.9%), proximal (4.2%), total (29.2%), extended total (ETG) (27.8%). Positive RMs were found in 13.2%, with 8.3% having positive longitudinal margins and 6.3% positive circumferential margins. Neoadjuvant-chemotherapy was completed by 73% of subjects. Poor tumour differentiation was seen in 59.7%, SR presence in 12.5%, and LP in 3.5%. Significant associations were noted between positive margins and LP (80%, p&amp;lt;0.001) and age (&amp;lt;65: 15%, &amp;gt;=65: 4%, p=0.028). ETGs had double the rate of positive margins (12.5%) than that of other gastrectomies (6.7%,p=0.314). Conclusion The overall positive longitudinal margin rate was higher than the national guideline, replicating NOGCA audits. Our hypothesis was not proved: although the longitudinal positive margin rate in ETGs was almost double that of other gastrectomies, this did not reach statistical significance. Positive margin rates were higher in younger patients, and those with LP. Further large-scale audit is urgently required to determine if the recommended margin rate is appropriate or whether it should be adjusted for factors such as tumour location, presence of LP and age when the risk of a positive margin is higher.

MS O06 - HPB The ORDEAL Study: A National Survey of Surgeon Operative Preferences for Resection of Duodenal Adenocarcinoma

Abstract Background Duodenal adenocarcinoma (DA) accounts for over 50% of all small bowel adenocarcinomas, however there is a paucity of data on outcomes, no UK guidelines for surgical management, and current national standards of practice are unknown. There is ongoing debate whether long-term survival, perioperative outcomes, resection margin, and lymph node yield differ between pylorus-preserving pancreaticoduodenectomy (PPPD) and classical PD (cPD) in proximal DA (D1/D2), and between PD and limited resection (LR) in distal DA (D3/D4). The study aimed to discern current standards of practice and identify underlying reasons for operative preferences for proximal and distal DA. Method An anonymised survey was included as part of the registration form for a wider multicentre retrospective study looking at outcomes following resection for proximal and distal DA on Google Forms®. The survey was distributed via direct surgeon email correspondence, weekly newsletters and surgical society endorsement by PSGBI. Responses were collected between February-June 2024 and responses were analysed with quantitative and qualitative (inductive thematic analysis) methods. Results Responses were received from 61 surgeons across 27 centres. For proximal DA, surgeons are more likely to consider a classical Whipple’s (93.4%) compared to PPPD (29.5%). For distal DA, surgeons are equally likely to consider LR (73.8%) as PD (classical Whipple’s -37.7%, PPPD - 41%). These preferences have mostly remained consistent over time. Key themes identified from thematic analysis included oncological considerations, morbidity, surgeon preference, tumour characteristics, standards of practice, patient factors and anatomical considerations, with the former two themes being the most prominent. Conclusion For proximal DA, cPD is preferred over PPPD and for distal DA, LR and PD are equally considered, with oncological and morbidity considerations largely influencing decision making. This qualitative data will be compared to actual practice following completion of the wider ORDEAL study to identify discrepancies in practice and possible effect on patient outcomes.

HPB SO41 - Does Adjuvant Chemotherapy Provide a Survival Benefit in Elderly Patients (≥70 years) with Pancreatic Cancer? A Retrospective Cohort-study

Abstract Background There is currently conflicting evidence surrounding the use of adjuvant chemotherapy (AC) for elderly patients (over 70 years) with pancreatic adenocarcinoma. Limited existing studies debate its effect on overall survival (OS) and relapse-free survival (RFS). The aim of this study is to assess whether adjuvant chemotherapy following pancreaticoduodenectomy provides a survival benefit in elderly patients with pancreatic cancer. Method A retrospective review including elderly adult patients, seventy years and older, who underwent a Whipple’s pancreatoduodenectomy for pancreatic adenocarcinoma between 1st January 2015 and 31st December 2020, at a tertiary HPB centre was performed. Information on baseline characteristics, preoperative assessment, histopathology, postoperative complications and course, and adjuvant chemotherapy were collected. Elderly patients who received AC were compared to those who did not undergo AC. Statistical analysis was performed using Jamovi 2.3. Results Sixty-eight patients were included with 44 (65%) receiving AC. There was no difference in age (p=0.72), sex (p=0.19), preoperative characteristics (all p&amp;lt;0.05), and resection margin (p=0.67) between the groups. There was no difference in complication rates (p=0.20), including Clavien-Dindo3+ (p=0.68). The length of hospital stay was shorter in the AC group, without statistical significance (15.7±11.9 vs 23.2±20.3 days, p=0.06). There was no difference in RFS between the groups (22.7±20 vs 15.4±23.6 months, p=0.18). However, patients who received AC had a significantly greater OS compared to those who did not (30.7±18.2 vs 18.6±22.2 months, p=0.02). Conclusion AC improved overall survival in elderly (≥70 years) patients with pancreatic adenocarcinoma. Whilst many elderly patients may not receive adjuvant chemotherapy due to postoperative complications and/or longer hospital stay, our study suggests age alone should not be a deciding factor when considering adjuvant chemotherapy in this cohort. A future large, multicentre prospective study is needed to further examine OS with the use of AC in elderly patients with pancreatic adenocarcinoma.

MS O11 - HPB Laparoscopic vs open liver resections for hepatocellular cancer in a tertiary care hepatobiliary unit; outcomes of cases over 10 years

Abstract Background Despite its established role in liver resection surgery, minimally invasive surgery is still not a favoured option in cases of hepatocellular cancer (HCC) due to perceived risks of intra- and post-operative surgical morbidity and poorer oncological outcomes. This study aims to look at the outcomes of liver resections performed for HCC cases over ten years comparing laparoscopic and open cohorts. Method A retrospective study including all liver resections for HCC cases performed in our tertiary care hepatobiliary unit between 2013 and 2022 (10 years) was conducted. Data on demographics, underlying degree of liver cirrhosis, types of liver resection and post-operative outcomes, including recurrence rates and resections margins were collected and reported using descriptive statistics. Survival analysis was performed with compared between these two groups with log rank test in GraphPad prism 10. Results 200 liver resections performed for HCC were grouped into laparoscopic and open cohorts containing 147 and 53 patients respectively. 21 (40%) laparoscopic cases had background liver cirrhosis as compared to 24 (16%) in open cases. Major liver resection comprised 9% and 43% of all cases and one and five patients had Grade B/C PHLF in laparoscopic and open groups. All 8 (4%) cases with 90-day mortality were from the open group. Negative resection margins (68% vs 71%), local recurrence (51% vs 47%) and overall survival (75 months vs 67 months (p=0.29)) were similar in laparoscopic and open groups, respectively. Conclusion Post-operative and oncological outcomes of liver resections for HCC were comparable in laparoscopic and open groups. Laparoscopic liver resections could be safely performed in patients with background liver cirrhosis.

OGC SO25 - Tumour Regression Grade (TRG) and Completeness of Resection in patients under esophagectomy for oesophageal Cancer

Abstract Background Oesophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma, is challenging due to its aggressive nature and delayed presentation. Neoadjuvant chemotherapy aims to downstage the tumour thus aids in surgery and improves patient outcomes. Complete resection with tumour free resection margins is crucial for cure and survival. Understanding the relationship between tumour regression grade (TRG) and completeness of resection helps improve outcomes in patients with oesophageal cancer. Method This retrospective study was conducted over a period of 4 years (2019-2023). It included all patients over 18 years of age who underwent oesophagectomy for either squamous cell carcinoma (SCC) or adenocarcinoma following neoadjuvant chemotherapy. Tumour Regression Grade (TRG) was defined by the histological report while R1 resection was defined as any margin less than 1 mm. Statistical analysis was performed to evaluate the incidence of complete and incomplete resections across the various TRG groups. Results Study included 214 patients (178 males, 36 females) with a median age of 67 (31-82) years. Of the 214 patients, 201 (93.9%) had adenocarcinoma and 13 (6.1%) had SCC. Complete resection was achieved in 136 patients (63.6%), while 78 (36.4 %) had incomplete resections. TRG distribution in the complete resection group was-TRG 1 (97.6 %), TRG 2 (76.5 %), TRG 3 (67.2 %), TRG 4 (56.1 %), and TRG 5 (31.9 %). The Chi-Square test indicated significant associations between TRG and resection completeness (Chi-Square = 44.229, p &amp;lt; .001; Likelihood Ratio = 51.804, p &amp;lt; .001; Fisher's Exact Test p &amp;lt; .001). Conclusion The study demonstrates a significant correlation between higher TRG scores and incomplete resections in esophagectomy patients’ post-neoadjuvant chemotherapy. We conclude TRG is an important prognostic indicator for surgical outcomes in oesophageal cancer.

HPB SO28 - Pre-operative Biliary Drainage in Pancreatic Adenocarcinoma and its Effect on Surgical Oncological Outcomes

Abstract Background Pre-operative biliary drainage (PBD) in patients undergoing pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been associated with a significantly increased risk of serious complications. This retrospective study investigated if PBD has a significant effect on lymphovascular (LVI) or perineural (PNI) invasion compared to direct surgery (DS). Method Data was collected retrospectively from patients undergoing PD for PDAC from 01/01/2014 to 30/12/2022. Patients were grouped according to whether they received any form of PBD or not. Patients’ T and N stage, as well as lymph node ratio (LNR), R status, Mortality, disease free (DFS) and overall survival (OS) were recorded. The primary outcome measure was lymph node ratio. Results A total of 87 patients were identified (48 PBD group vs 39 DS group), with a mean age of 68. The median LNR was 0.2 in PBD vs 0.21 in DS Group (p=0.87). There was no significant difference in median DFS (310 days PBD vs 285 DS p=0.94) or median OS (513 days PBD vs 515 DS p=0.39). PBD was not associated with a greater incidence of LVI (67% PBD vs 69% DS p=0.8), or PNI (94% PBD vs 97% p=0.41). PBD did not have a significant effect on resection margin status (p=0.75). Conclusion Despite evidence in the literature on its effects on the rate of complications, PBD has not been shown to have an effect on LVI or PNI, disease progression, nor overall survival in our patient group.

OGC SO04 - Impact of COVID-19 on Decision-making and Survival in Esophago-Gastric Cancer Treatment: Insights from a Multidisciplinary Approach

Abstract Background The COVID-19 pandemic necessitated rapid adaptation in healthcare delivery, affecting cancer care pathways. This study assesses the impact of these changes on multidisciplinary team (MDT) decision-making and survival outcomes in esophago-gastric cancer patients across pre-pandemic, peak pandemic, and post-pandemic periods. Method A retrospective cohort study involving patients referred to a UK tertiary EG cancer center during distinct six-month intervals mirroring the pandemic's evolution. Analysis focused on MDT recommendations, treatment pathways, and two-year survival rates, comparing deviations from standard care across periods. Results The study revealed a significant reduction in patient referrals and expedited treatment decisions during the pandemic peak, with a shift towards palliative care in post-pandemic cases. Although no statistically significant difference in two-year survival rates was observed, the post-pandemic period showed an increase in tumor aggressiveness and positive resection margins, suggesting potential long-term impacts of delayed diagnosis and treatment. Conclusion COVID-19 has significantly influenced MDT decision-making and patient pathways in esophago-gastric cancer care, underlining the necessity of resilient healthcare systems. Despite maintaining survival rates, the observed increase in tumor aggressiveness post-pandemic highlights the critical need for uninterrupted cancer diagnosis and treatment services during global health emergencies.

HPB SO69 - Comparison of radical antegrade modular pancreatosplenectomy with standard pancreatosplenectomy for left sided pancreatic cancer

Abstract Background Long term survival of patients undergoing distal pancreatosplenectomy for left sided pancreatic cancer has not been satisfactory owing to inability to achieve negative resection margins. Radical antegrade modular pancreatosplenectomy (RAMPS) has been designed to achieve better margin resection and better lymph node clearance compared to the standard distal pancreatosplenectomy (SDP) for left sided pancreatic cancer. This results in better oncological outcomes and patient survival rates. The aim of this study was to compare clinical outcomes from RAMPS and SDP. Method Literature search was performed to identify studies published in Pubmed, Embase, Cochrane library and google search. 13 Studies comparing RAMPS versus standard method of distal pancreatecetomy were included in the final meta-analysis. Revman 5.4 was used to perform the analysis and random effects model was used with results shown on forest plot. A total of 1450 patients were enrolled in the meta analysis with 685 in RAMPS and 765 patients in SDP group. R0 resection rate, recurrence rate, better overall survival and number of harvested lymph nodes were taken as primary outcomes. Results RAMPS was associated with better overall survival than SDP (HR-0.62, 95% CI - 0.38-0.91, p=0.03). The recurrence rate (OR-0.68, 95% CI 0.47-0.97, p=0.04) was significantly less. R0 resection rate was higher in RAMPS but did not reach statistical significance (OR-1.47 CI0.93-2.3, p=0.10). Complications notably pancreatic fistula Showed favourable results in RAMPS along with other variables such as hospital stay, operative stay and blood loss but didn’t reach statistical Significance. Conclusion This study clearly signifies the importance of RAMPS being able to achieve higher R0 resection rate as well as less complications which results in better surgical and long term clinical outcomes for the patients. With more expertise and surgical training, this novel procedure promises to be a more safer and feasible technique than the conventional pancreatosplenectomy.

HPB SO54 - Outcomes of Isolated Bile Duct Resection for Cholangiocarcinoma; More Than 15 Years Experience in a Single Tertiary HPB Centre

Abstract Background Cholangiocarcinoma of the extrahepatic biliary tree usually requires a major resection to achieve clear margins with adequate lymphadenectomy. For perihilar tumours this involves extended liver resection with bile duct resection whilst distal tumours require pancreaticoduodenectomy. Occasionally a combination of both (hepato-pancreaticoduodenectomy) is required. These procedures are associated with high morbidity and mortality. In a small number of patients, cholangiocarcinoma is confined to the extrahepatic bile duct with no involvement of the liver or pancreas and a bile duct resection alone is an option. We reviewed the outcomes of patients who underwent bile duct resection for cholangiocarcinoma in our unit. Method We identified all patients who underwent bile duct resection and hepaticojejunostomy for cholangiocarcinoma between June 2007 and June 2023 in our centre from a prospectively maintained database. Patient demographics, complications, histology, resection margin status, follow-up, recurrence, and survival were recorded. Time to recurrence and overall survival were analysed using Kaplan Meier analysis. Results Thirteen patients underwent bile duct resection and hepaticojejunostomy for cholangiocarcinoma. 12 (92%) were male and the median (range) age was 72 (41-82). No patients received neoadjuvant treatment. 3 (23%) patients developed postoperative complications with 1 (7.7%) perioperative mortality. R0 margin was achieved in 6 (46%). The median (range) postoperative stay was 7 (5-25) days. 8 (61.5%) patients received adjuvant chemotherapy. 7 patients (53.8%) developed recurrent disease at a median of 12 (IQR 8-54) months following surgery. The most common sites of recurrence were the liver (23.1%) followed by local recurrence (15.4%). The median survival was 38 (IQR 20-95) months. Conclusion Extrahepatic bile duct resection with hepaticojejunostomy is an option for patients with cholangiocarcinoma of the extrahepatic bile duct without macroscopic involvement of the liver or pancreas. In our series this procedure was associated with a low morbidity and perioperative mortality with acceptable recurrence rates and overall survival despite only modest R0 resection rates. Isolated bile duct resection with hepaticojejunostomy should be considered for tumours without macroscopic involvement of the liver or pancreas, especially in patients of borderline fitness for a more extensive resection.

Tailored resection for persistent extramural vascular invasion in locally advanced rectal cancers.

Extramural vascular invasion (EMVI) is a bad prognostic feature in rectal cancer and cancers that remain EMVI positive after neoadjuvant therapy are at high risk for having involved circumferential resection margins. Conventional total mesorectal excision (TME) resections are inadequate in such cases and often lead to positive margins. We propose a technique for the surgical management of locally advanced tumours with persistent EMVI after neoadjuvant therapy. Ten such tumours were resected using a "beyond TME" (b-TME) approach with or without lateral pelvic lymph node dissection or seminal vesical excision. A b-TME approach, customized to the anatomy of the tumour allowed for an R0 resection with a negative circumferential resection margin (CRM) in all 10 cases. A tailored b-TME approach can achieve good results in cases at high risk for CRM involvement.

The Evolving Role of Neoadjuvant Radiation Therapy in Pancreatic Adenocarcinoma

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

SURG-57. FLUORESCENCE LIFETIME IMAGING (FLIM) PROVIDES HIGHLY ACCURATE, DYE-FREE TUMOR MARGIN DETECTION DURING GLIOMA RESECTIONS

Abstract INTRODUCTION Fluorescence guided tumor margin detection is an important tool to enhance the extent of resection for gliomas. Existing dyes, such as 5-ALA, require planned administration, surgical resection in dark conditions, and are only effective for high-grade tumors. We have developed a novel laser scanning probe to assess tissue autofluorescence decay (lifetime) which allows tumor margin detection without exogenous dyes and under normal room light conditions. This technology has been optimized for margin detection in low-grade and high-grade gliomas. METHODS Patients undergoing craniotomy for resection of gliomas were enrolled. During resection of the final tumor margin, multiple 1x1 mm regions were scanned with FLIm and biopsied for evaluation by a neuropathologist. FLIm data and ground truth pathology were processed by a machine-learning algorithm to develop classifiers for the FLIm data. Classifiers were then applied to the full data set to determine the accuracy of FLIm predictions. RESULTS 12 patients with non-enhancing (LGG) and 25 patients with enhancing (HGG) tumors were enrolled, with a total of 228 biopsies obtained. For LGG, sensitivity of FLIm for detection of residual tumor was 0.89 (95% CI 0.8-0.98) with a specificity of 0.92 (95% CI 0.86-0.97), resulting in a positive predictive value of 0.76 and negative predictive value of 0.96 with an overall accuracy of 0.91. For HGG, sensitivity of FLIm for detection of residual tumor was 0.92 (95% CI 0.84-1.0) with a specificity of 0.95 (95% CI 0.91-0.99), resulting in a positive predictive value of 0.90 and negative predictive value of 0.96 with an overall accuracy of 0.94, exceeding reported values for 5-ALA. CONCLUSION FLIm can distinguish between residual low and high-grade glioma and normal brain at resection margins with very high sensitivity and specificity. This quantitative technology does not require administration of exogenous dyes and can be used under normal room light illumination.

SURG-18. INNOVATIVE DRUG-DEVICE COMBINATION FOR THE PHOTODYNAMIC TREATMENT OF PRIMARY GLIOBLASTOMA (GBM) PATIENTS

Abstract Despite advances in neurosurgical technology and techniques, the survival rate of GBM patients has remained relatively unchanged. The main treatments for GBM are associated with difficulties resulting from incomplete tumor resection and recurrence. In such situations, Photodynamic Therapy (PDT) is increasingly popular as an advanced therapeutic strategy, characterized by fewer side effects, minimal toxicity, and more controlled treatment. 5-aminolevulinic acid hydrochloride, (5-ALA HCl) has been used for years as a photosensitizing drug for the intraoperative visualization of GBM tumor tissue, enabling a more complete tumor resection. We demonstrated that, after such fluorescence-guided surgery, a laser light of specific 635 nm wavelength can additionally induce specific tumor cell death via the production of reactive oxygen species. This 5-ALA HCl–based PDT provides an antitumor effect within the tumor resection margins where recurrences occur in almost all patients. After performing pilot studies in over 20 patients with primary GBM, leading to positive safety and survival signals, we designed a new drug-device combination for this specific PDT procedure. It consists of Pentalafen ®, 5-ALA HCl administered orally to the patient before surgery, combined to Heliance®, a balloon device, inflated intraoperatively into the resection cavity, and connected to a controller (laser system) via an optical fiber to produce the light that illuminates the resection margins. A dedicated algorithm enables the duration of the illumination to be automatically computed from the tumor volume. This procedure adds an average of 30 minutes to the neurosurgery and can thus be fully integrated into the standard of care for primary GBM. This new drug-device combination is currently evaluated in a US phase 1 trial (NCT05736406) evaluating the feasibility of different light regimen treatments with the aim of delaying GBM recurrence and improving overall survival. If data is confirmed, it could be applicable to other CNS and solid tumors.

TMIC-59. ENTANGLED: THE INTERPLAY OF CELLULAR PLASTICITY AND NEURONAL SIGNALING IN BRAIN CANCER PROGRESSION

Abstract The interplay between two recently proposed hallmarks of cancer, namely dedifferentiation/transdifferentiation and altered neuronal signaling, may dictate the spatiotemporal coupling between neurons and astrocytes. Synaptic activity correlates with brain cancer progression and further influences the directionality of metabolites. Through phenotypic plasticity, brain parenchymal cells may dedifferentiate in a manner that determines the directionality of metabolites, thereby altering plasticity and exerting selective pressure on the immune microenvironment within the brain. Therapeutic advancements in brain cancers, including maximizing surgical resection margins and Chimeric Antigen Receptor (CAR) T-cell therapy, have their own limitations. Thus, understanding the interplay between dedifferentiation/transdifferentiation and its role in dictating altered neuronal signaling to modulate the brain tumor microenvironment may provide novel targets for improving prognosis and limiting therapeutic toxicity.

Assessment of Optimal Treatment Strategies and Their Outcomes in T3N1 Rectal Cancers.

Background:This study compares the outcomes of a surgery first vs a neoadjuvant treatment strategy in T3N1M0 rectal cancers. Methods:This was a single-centre retrospective cohort study of patients admitted for curative treatment of T3N1 rectal cancer. Patients with pre-treatment T3N1 and pathological T3N1 disease were included in the study. Patients were divided into two groups depending on whether they had surgery or neoadjuvant therapy as their initial phase of treatment. Primary outcome measures were local recurrence and distant recurrence. Secondary outcomes were disease-free survival (DFS) and overall survival (OS). Tabulated results were analyzed with appropriate statistical tests. Results:One hundred and ten patients were initially selected. Fourty-eight were finally included after excluding patients who did not meet the staging criteria or were not eligible for curative treatment. Twenty-nine patients underwent surgery, and 19 patients with neoadjuvant therapy as their first treatment. No local recurrence was noted in either group, with a distant recurrence noted in group 2 (6.9%) and group 1 (5.26%) cases among the surgery-first and neoadjuvant-first groups, respectively. Disease-free survival and overall survival were 29.5 and 30 months for the surgery-first group and 22 and 22 months for the neo-adjuvant group, respectively. Conclusions:Outcomes in the surgery-first group were non-inferior to that of the neoadjuvant group. A threatened circumferential resection margin (CRM) on pretreatment staging warrants neoadjuvant therapy to ensure an R0 resection. Extramural vascular invasion (EMVI), being a negative prognostic factor, doesn't preclude a surgery-first approach.

The clinical application value of mixed reality in robotic laparoscopic partial nephrectomy

PurposeRobot-assisted laparoscopic partial nephrectomy (RAPN) has become a key technology in the treatment of renal tumors. Effective preoperative planning and precise intraoperative navigation are critical to a successful surgical outcome. This study aimed to evaluate the clinical application value of mixed reality (MR) in robotic nephron-sparing partial nephrectomy for patients with renal tumors of different complexity based on the R.E.N.A.L. score.Patients and methodsA retrospective analysis was conducted on 68 eligible patients with renal cancer who underwent RAPN at The Second Affiliated Hospital of Nanchang University from January 2021 to December 2023, with postoperative pathology confirmation. Patients were divided into two groups: the MR group, with 28 cases, and the traditional imaging (control) group, with 40 cases. All patients underwent mid-abdominal CT plain scans and enhancements. The MR group utilized three-dimensional reconstruction of CT data and employed 3D tablets and HoloLens glasses for preoperative discussions, surgical planning, and intraoperative guidance. Collect clinical data and metrics to assess surgical outcomes, as well as evaluate performance in areas such as preoperative discussions, doctor-patient communication, surgical planning, and intraoperative navigation.ResultsCompared to robot-assisted partial nephrectomy in the control group, the MR group experienced a reduction in operation time by approximately 30 min [(135.89 ± 23.494) min vs. (165.00 ± 34.320) min, P&amp;lt; 0.001)] and a decrease in ischemia time by around 2.5 min [(20.36 ± 3.956) min vs. (23.80± 6.889) min, P = 0.02)]. Within the subgroup with a R.E.N.A.L. score of less than 7 points, the MR group only showed a significant reduction in operation time [(134.55 ± 150.190) min vs. (150.19 ± 28.638) min, P = 0.045], with no notable differences in other parameters. For the subgroup with a R.E.N.A.L. score of 7 points or higher, the MR group exhibited shorter operation time [(140.83 ± 25.183) min vs. (195.77 ± 23.080) min, P&amp;lt; 0.001] and reduced warm ischemia time [(21.17 ± 2.714) min vs. (28.85 ± 7.570) min, P = 0.029]. Additionally, there was less estimated blood loss [(53.33 ± 5.164) min vs. (114.62 ± 80.376) min, P = 0.018]. All patients had negative resection margins, indicating equivalent therapeutic outcomes between the two groups.ConclusionIn comparison to traditional RAPN, MR technology demonstrates the ability to decrease operation time and warm ischemia time all the while maintaining equivalent curative outcomes. Additionally, it enhances preoperative discussions, doctor-patient interactions, preoperative strategizing, and intraoperative navigation, particularly excelling in complex renal tumor cases of RAPN, where its benefits are most pronounced.

Relationship between bone union and degree of bone marrow fibrosis at resection margins of advanced mandibular ORN

BackgroundThe pathological evaluation of cancellous bone at resection margins of mandibular osteoradionecrosis (ORN) has not been well elucidated. Here, we developed a unique classification system for evaluating the degree of bone marrow fibrosis, one of most common pathological features, in patients with mandibular ORN, based on which we investigated its relationship with treatment outcome.MethodsThis study included 15 patients who underwent mandibulectomy and free fibula osteocutaneous flap reconstruction. The extent of mandibulectomy was determined, with safety margins of approximately 10 mm from the apparent osteolytic areas on preoperative computed tomography image. Special staining was performed on thin sections from center of the osteolytic areas (medial area) and bilateral resection margins, and the degree of bone marrow fibrosis was evaluated and investigated its relationship with presence of bone union as a treatment outcome.ResultsThe degree of bone marrow fibrosis of medial area was significantly higher than those of resection margins. Although most resection margins had collagen fibers which indicate severe fibrosis, all transferred fibula flaps achieved bone union.ConclusionWhen mandibulectomy is performed with safety margins of approximately 10 mm from the apparent osteolytic areas, all transferred fibula flaps achieved bone union regardless of the degree of bone marrow fibrosis at resection margin. In other words, the association between severe bone marrow fibrosis at resection margins and treatment outcome was not seen.Clinical RelevanceSetting safety margins of approximately 10 mm may achieve bone union, but further study is needed.